Rosuvastatin calcium is a selective inhibitor of HMG-CoA reductase. It was developed by AstraZeneca company, and has been marketed in many countries and regions including the United States, Japan, Europe and China, with the trade name “CRESTOR” (trade name in Chinese: KeDing). It has a chemical name of calcium bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxy-hept-6-enoate], and has a structure of formula A. Rosuvastatin calcium is a highly effective hypolipidemic drug, and can be used for treating primary hypercholesterolemia and mixed type lipodystrophy as well as homozygous familial hypercholesterolemia. It is highly favored due to its advantages of high efficiency and low toxic side effects, and therefore has a very broad prospect.

Currently there have been many patent documents reporting the synthetic processes of rosuvastatin calcium and the preparation of the key intermediates. The processes can be generally classified into the following two categories: (1) introducing an aldehyde group to the pyrimidine core, making the side chain as a Wittig reagent, obtaining the trans olefin intermediate via Wittig reaction, which is further converted to the product; (2) introducing a Ylide reagent or other reagents to the pyrimidine core, making the side chain as an aldehyde compound, obtaining the trans olefin intermediate via Wittig reaction, which is further converted to the product. Several processes suitable for industrial production are summarized below.
Patent application WO 2004103977A reports that the key trans intermediate, compound 3, is obtained with a selectivity of about 50:1 through olefination reaction of compound 1 with the side chain aldehyde in the presence of an alkali. Compound 3 is subjected to deprotection, hydrolysis and calcium salt formation to give rosuvastatin calcium. The patent application also seeks protection of the key starting material and the intermediates 1 and 3.

Patent application US 2005/0124639A1 reports conducting the olefination reaction of the quaternary phosphonium compound 4 with the aldehyde side chain 5, and obtaining the key trans intermediate compound 6 with a medium selectivity. Compound 6 is subjected to deprotection, hydrolysis and calcium salt formation to give rosuvastatin calcium, wherein R1, R2 and R3 in the quaternary phosphonium may be alkyl or aromatic groups, and the anion may be halogen, trifluoroacetyl, methylsulfonyl or the like. The patent application also seeks protection of the key starting material 4.

Patent application WO 2010023678 reports obtaining the key intermediate compound 3 through Julia olefination reaction of raw material 7 with compound 2, and then obtaining rosuvastatin calcium through a similar process.

Patent application EP 0521471A1 reports the preparation of rosuvastatin calcium from pyrimidine aldehyde compound 8 and compound 9 through the steps of Wittig reaction, deprotection, selective reduction and hydrolysis. Patent application CN 200510026350 makes further improvements to said process.

Although rosuvastatin calcium can be industrially produced by the above routes, there are still problems in many aspects such as synthesis of raw materials, selectivity of the reactions, separation and purification of the intermediates and the final products. Accordingly, it is very necessary to develop a preparation method with low costs, simple operations, and high product qualities.